Chronic hypoxia upregulates connexin43 expression in rat carotid body and petrosal ganglion

Abstract

Recent studies have demonstrated that oxygen-sensitive type I cells in the carotid body express the gap junction-forming protein connexin43 (Cx43). In the present study, we examined the hypothesis that chronic exposure to hypoxia increases Cx43 expression in type I cells as well as in chemoafferent neurons in the petrosal ganglion. Immunocytochemical studies in tissues from normal rats revealed diffuse and granular Cx43-like immunoreactivity in the cytoplasm of type I cells and dense punctate spots of immunoreactive product at the margins of type I cells and near the borders of chemosensory cell lobules. Cx43-like immunoreactivity was not detectable in petrosal ganglion neurons from normal animals. After a 2-wk exposure to hypobaric (380 Torr) hypoxia, Cx43 immunostaining was substantially enhanced in and around type I cells. Moreover, chronic hypoxia elicited the expression of Cx43-like immunoreactivity in the cytoplasm of afferent neurons throughout the petrosal ganglion. Quantitative RT-PCR studies indicate that chronic hypoxia evokes a substantial increase in Cx43 mRNA levels in the carotid body, along with a marked elevation of Cx43 expression in the petrosal ganglion. Increased Cx43 expression and gap junction formation in type I cells and sensory neurons may contribute to carotid body adaptation during sustained stimulation in extreme physiological conditions.

Hypoxia and Stretch Regulate Intercellular Communication in Vascular Smooth Muscle Cells Through Reactive Oxygen Species Formation

“…Other investigators have shown Cx43 expression can increase (ie, in the carotid body and petrosal ganglion) 20 or decrease (ie, in cultured astrocytes) 21 in response to hypoxia; however, the underlying mechanism of this regulation remains unknown. Remarkably, by suppressing the hypoxia-induced elevation in ROS formation in smooth muscle cells by either a mitochondrial complex I inhibitor (rotenone) or a glutathione peroxidase mimic (ebselen), the ensuing rise in Cx43 protein levels and gap junction channel permeability could be largely prevented.…”

The influence of chronic hypoxia upon chemoreception

“…However, P2X 2 blockaded did not completely eliminate the response to hypoxia in either condition indicating that ATP acts in concert with other excitatory mechanisms in the carotid body. This could be an excitatory neurotransmitter, such as ACh discussed above, or perhaps enhanced electrical coupling between glomus cells and afferent nerve terminals considering that chronic hypoxia up-regulated gap junction proteins (connexin-43) in carotid bodies (Chen et al, 2002a).…”

The Selective Degradation of Synaptic Connexin 43 Protein by Hypoxia-induced Autophagy Impairs Natural Killer Cell-mediated Tumor Cell Killing

“…It has been reported that hypoxia regulates Cx43 expression and channel activity in different cell models (20,21). However, no data are currently available addressing the role of Cx43 channels in melanoma cells in the context of the hypoxic microenvironment and their putative involvement in tumor cell susceptibility to NK cell-mediated lysis.…”